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Uvod Lokalna terapija antibiotskim preparatima predstavlja pogodan način prevencije i/ili lečenja određenih infekcija kože, ali ima i niz ograničenja koja su vezana kako za lekovite supstance sa antimikrobnim delovanjem, tako i za podloge koje se koriste kao njihovi nosači. Pored porasta rezistencije bakterija, nedostatak dermalne primene antibiotika je i njihova slaba penetracija u kožu, ali i toksičnost nekih od njih prema humanim ćelijama. Usled toga, nameće se potreba za pronalaženjem novih supstanci sa antimikrobnom aktivnošću širokog spektra dejstva i poboljšanom dermalnom raspoloživošću/bezbednosnim profilom. Kao potencijalni izvori ovakvih supstanci sve više se istražuju lišajevi, među kojima se naročito istakla Usnea barbata (L.) Weber ex F.H. Wigg., Parmeliaceae (jevrejska ili lišaj brada). Iako se brojna biološka svojstva lišaj brade pripisuju usninskoj kiselini, novija istraživanja ukazala su na neke prednosti upotrebe njenog ekstrakta dobijenog primenom natkritičnog ugljen-dioksida (CO2) u odnosu na ovu supstancu per se. Sa druge strane, poznato je da su emulzioni sistemi (naročito kremovi), kao najpopularniji nosači lekovitih supstanci u dermatološkim preparatima, često stabilizovani tradicionalnim anjonskim/nejonskim mešanim emulgatorima, koji mogu izazvati neželjene reakcije, posebno na oboleloj koži. Pored toga, značajan uticaj kozmetičke industrije na dermofarmaciju je, uz porast zabrinutosti za zaštitu životne sredine, stavio u fokus istraživanja savremenih emulgatora povoljnijeg ekološkog i dermatološkog profila, koji istovremeno mogu da obezbede poboljšane senzorne osobine kremova za primenu na koži. Cilj istraživanja Cilj istraživanja ove doktorske disertacije bio je razvoj emulzionog sistema tipa hidrofilnog krema sa biorazgradivim alkil poligukozidnim (APG) emulgatorima prirodnog porekla, kao nosača za ekstrakt talusa U. barbata sa kvantifikovanom usninskom kiselinom, kroz procenu koloidne strukture, fizičke stabilnosti i biofarmaceutskih kar, Introduction Local therapy with antibiotic preparations represents the preferable way of prevention and/or treatment of some skin infections but also has a number of limitations connected to antimicrobial agents on one the hand and vehicles used as their carriers, on the other. Aside from bacterial resistance growth, a major problem regarding dermal application of antibiotics is their poor penetration into the skin, and also toxicity to human cells, documented for some of them. Therefore, there is a growing interest in the research concerning new substances with broad-spectrum antimicrobial activity and improved dermal availability/safety profile. Lately, various lichens are being intensively investigated as potential sources of such substances, among which Usnea barbata (L.) Weber ex F. H. Wigg., Parmeliaceae (old man’s beard) has been singled out, as one of the most frequently investigated. Although various biological properties of old man’s beard have been attributed to usnic acid, recent research suggested certain benefits of usage of its extract obtained using supercritical carbon dioxide (CO2), compared to this compound per se. On the other hand, it is well established that the emulsion systems (particularly creams), as the most popular carriers in dermatological preparations, are often stabilized using conventional anionic/non-ionic emulsifiers, known to cause adverse effects, especially in the diseased skin. Besides that, a major impact of the cosmetic industry on dermopharmacy, alongside with the growing environmental concerns, has put in the focus research of contemporary emulsifiers with favorable dermatological and ecological profile, which are also able to provide enhanced sensory properties of creams for skin application. Aim The aim of this doctoral dissertation was the development of an emulsion system of hydrophilic cream type based on biodegradable alkyl polyglucoside (APG) emulsifiers, as a potential carrier for the extract of the talus of U. barb

Topical treatment of skin infections is often limited by drawbacks related to both antimicrobial agents and their vehicles. In addition, considering the growing promotion of natural therapeutic products, our objective was to develop and evaluate naturally-based emulsion system, as prospective topical formulation for skin infections-treatment. Therefore, alkyl polyglucoside surfactants were used for stabilization of a vehicle serving as potential carrier for supercritical CO2-extract of Usnea barbata, lichen with well-documented antimicrobial activity, incorporated using two protocols and three concentrations. Comprehensive physicochemical characterization suggested possible involvement of extracts particles in stabilization of the investigated system. Raman spectral imaging served as the key method in disclosing extracts particles potential to participate in the microstructure of the tested emulsion system via three mechanisms: (1) particle-particle aggregation, (2) adsorption at the oil-water interface and (3) hydrophobic particle-surfactant interactions. Stated extract-vehicle interaction proved to be correlated to the preparation procedure and extract concentration on one hand and to affect the physicochemical and biopharmaceutical features of investigated system, on the other hand. Thereafter, formulation with the best preliminary stability and liberation profile was selected for further efficiency and in vivo skin irritation potential evaluation, implying pertinent in vitro antimicrobial activity against G+ bacteria and overall satisfying preliminary safety profile.

This paper describes design and evaluation of parenteral lecithin-based nanoemulsions intended for brain delivery of risperidone, a poorly water-soluble psychopharmacological drug. The nanoemulsions were prepared through cold/hot high pressure homogenization and characterized regarding droplet size, polydispersity, surface charge, morphology, drug-vehicle interactions, and physical stability. To estimate the simultaneous influence of nanoemulsion formulation and preparation parameters-co-emulsifier type, aqueous phase type, homogenization temperature-on the critical quality attributes of developed nanoemulsions, a general factorial experimental design was applied. From the established design space and stability data, promising risperidone-loaded nanoemulsions (mean size about 160 nm, size distribution LT 0.15, zeta potential around -50 mV), containing sodium oleate in the aqueous phase and polysorbate 80, poloxamer 188 or Solutol (R) HS15 as co-emulsifier, were produced by hot homogenization and their ability to improve risperidone delivery to the brain was assessed in rats. Pharmacokinetic study demonstrated erratic brain profiles of risperidone following intraperitoneal administration in selected nanoemulsions, most probably due to their different droplet surface properties (different composition of the stabilizing layer). Namely, polysorbate 80-costabilized nanoemulsion showed increased (1.4-7.4-fold higher) risperidone brain availability compared to other nanoemulsions and drug solution, suggesting this nanoemulsion as a promising carrier worth exploring further for brain targeting.

The objectives of this study were to prepare films from submicron chitosan/Eudragit((R)) L100-55 polyelectrolyte complexes (CH/EL PEC) and to assess the influence of CH molecular weight and CH/EL mass ratio on their structure and drug-release properties. The films were obtained by a simple, environmentally friendly, casting/solvent evaporation method and the verapamil hydrochloride (VH) was used as model drug. Submicron size, narrow size distribution, and acceptable stability of CH/EL PECs were confirmed by DLS and laser Doppler microelectrophoresis. SEM analysis revealed nonporous inner structure and flat surface of the films. Interactions between comprising polymers and formation of CH/EL PEC were established by DSC and FT-IR spectroscopy. In vitro swelling and drug release studies revealed the pH sensitivity of the films, with burst drug release in acidic conditions (pH 1.2) and sustained release in phosphate buffers pH 5.8, 6.8, and 7.4. The slowest VH release was achieved from the films prepared from equal amounts of EL and CH of higher molecular weight, confirming the significance of the CH/EL ratio and CH molecular weight on their ability to sustain drug release. The obtained results suggested that presented, simple, and eco-friendly preparation procedure can be used to obtain pH-sensitive CH/EL PEC films with a promising potential as drug carriers.

This paper describes design and evaluation of parenteral lecithin-based nanoemulsions intended for brain delivery of risperidone, a poorly water-soluble psychopharmacological drug. The nanoemulsions were prepared through cold/hot high pressure homogenization and characterized regarding droplet size, polydispersity, surface charge, morphology, drug-vehicle interactions, and physical stability. To estimate the simultaneous influence of nanoemulsion formulation and preparation parameters-co-emulsifier type, aqueous phase type, homogenization temperature-on the critical quality attributes of developed nanoemulsions, a general factorial experimental design was applied. From the established design space and stability data, promising risperidone-loaded nanoemulsions (mean size about 160 nm, size distribution lt 0.15, zeta potential around -50 mV), containing sodium oleate in the aqueous phase and polysorbate 80, poloxamer 188 or Solutol (R) HS15 as co-emulsifier, were produced by hot homogenization and their ability to improve risperidone delivery to the brain was assessed in rats. Pharmacokinetic study demonstrated erratic brain profiles of risperidone following intraperitoneal administration in selected nanoemulsions, most probably due to their different droplet surface properties (different composition of the stabilizing layer). Namely, polysorbate 80-costabilized nanoemulsion showed increased (1.4-7.4-fold higher) risperidone brain availability compared to other nanoemulsions and drug solution, suggesting this nanoemulsion as a promising carrier worth exploring further for brain targeting.

Context: Approaching of pharmaceutical and cosmetic industries in some aspects inevitably influence formulation of topical pharmaceuticals, urging researchers to introduce novel excipients with proven benefits over traditional ones. In that context, alkyl polyglucosides (APG) emerge as prominent natural-origin emulsifiers with numerous favorable features (biodegradability, dermatological acceptability, desirable sensory properties). Objective: To evaluate APG-stabilized bases (alone and upon addition of isopropyl alcohol) and their impact on skin performance. A simultaneous in vitro/in vivo skin absorption study was conducted to evaluate whether the tape stripping technique could be recommended as an in vivo tool for skin penetration assessment during formulation optimization process. Materials and methods: After a comprehensive physicochemical characterization, biopharmaceutical properties of APG-bases versus reference ones were assessed through a combined in vitro (release/permeation) and in vivo approach. Results and discussion: Physicochemical characterization revealed substantial difference in structural ordering due to the formation of various mesomorphic phases. The enhancer-loaded APG base resulted in significantly higher drug levels at all depths into the stratum corneum, indicating that the selected enhancer along with specific colloidal structure has increased the extent of drug delivery. Conclusion: Results recommend the investigated emulsifier for stabilization of topical drug delivery systems, not only for their ability to sustain the addition of isopropyl alcohol which proved to be a valuable enhancer, but also satisfactory skin absorption and tolerability when compared to samples stabilized by conventional emulsifier. Tape stripping proved to be a useful and yet inexpensive tool for in vivo trials, able to discriminate subtle differences in dermal availability.

Context: Alkyl polyglucoside surfactants (APG) remain prominent natural origin stabilizers offering a prospect of combining satisfactory stability with mild dermatological properties and complete biodegradability. Objective: With the purpose of adjusting the dose to a patient's needs, dilution of commercial corticosteroid formulations is a practice which may modify efficacy uncontrolledly. The rational of the study was to investigate whether a simple change in ready-to-use bases (co-solvent addition) could address these needs in a more predictive manner. Methods: Hydrocortisone (HC) delivery from such emulsion systems was comparatively assessed employing two in vivo methods: the established human skin blanching assay versus skin stripping technique. Results: HC permeation data obtained after three dose durations showed better overall performance of the APG-stabilized bases relative to reference ones. Although the solubility study showed that all the assessed active samples retained equal thermodynamic activity, diverse HC permeation/penetration implies the importance of the applied base's colloidal structure and/or changes endured. Isopropyl alcohol (IPA) addition offered faster drug penetration enhancement, while glycerol as a moisturizing agent influenced HC penetration through the increase in skin hydration. Conclusion: Although the performed in vivo methods cannot be considered alternative, skin stripping technique proved to be a cost-efficient mode of percutaneous penetration assessment, providing additional information on vehicle-skin interactions.

Skin permeation and penetration assessment is important not only for determining efficacy of a topical product, but also when comparing different formulations during development. This chapter reviews methods for dermal availability assessment of delivery systems, with their advantages and shortcomings, and examples of their practical application with Alkyl Polyglucoside-based preparations. Alkyl Polyglucosides are used in many different delivery systems with various model actives. Systems stabilized with Alkyl Polyglucoside surfactants provide highly satisfactory cutaneous delivery compared with reference samples. This is mainly attributed to the characteristic APG-based colloidal structure and its ability to provide a combined enhancing effect with co-solvents. Microemulsions for dermal/transdermal delivery are also becoming popular due to their high solubilization potential. Alkyl Polyglucoside surfactants are also being considered for development of nanosystems.

Uvod Aktuelna farmakoekonomska situacija ima za posledicu čest nedostataklekova u potrebnim dozama/jačinama, a za neke lekovite supstance nisu odabranipogodni nosači. Značaj primene odgovarajućeg vehikuluma/podloge naročito je izraženu slučaju lekova koji se primenjuju na koži. Ova grupa lekova podložna je i uticajimakoji dolaze iz kozmetičke industrije, a odnose se na zadovoljavajući izgled, teksturu isenzorne karakteristike nosača, što se direktno reflektuje u kojoj meri će se pacijentipridržavati propisanoj terapiji. Nedostatak lekova na tržištu može se prevazići izradomlekova u apoteci čime se, čak i u zemljama sa veoma razvijenom farmaceutskomindustrijom, ponovo potencira značaj znanja i veština farmaceuta u ex tempore izradilekova. Iz tog razloga, prepoznata je potreba za inoviranjem sastava takvih lekova, presvega uvođenjem formulacija sa savremenim farmaceutskim ekscipijensima. S drugestrane, ostaje otvoreno pitanje procene dermalne raspoloživosti ovakvih lekova, sobzirom da regulatorno prihvaćene metode nisu univerzalno primenljive (poputograničene primenljivosti vazokonstriktornog testa na lekove iz grupe kortikosteroida)ili se smatraju neracionalnim u fazi razvoja formulacije (podrazumevaju značajnaulaganja i veliki broj ispitanika).Cilj istraživanja Cilj istraživanja ove disertacije bio je razvoj formulacije,fizičkohemijska i biofarmaceutska karakterizacija emulzionih sistema (podloga)stabilizovanih prirodnim mešanim emulgatorom tipa alkil poliglukozida (APG), sastavacetostearil glukozid i cetostearil alkohol, koji je od skora sertificiran kao farmaceutskiekscipijens. Razvijene formulacije poslužile su kao modeli za razvoj i optimizacijuprotokola metode sa adhezivnim trakama (tape stripping metode) kao perspektivne invivo tehnike za ispitivanje penetracije lekova kroz kožu, uz sprovođenje korelacije datihrezultata sa onim dobijenim prihvaćenim in vitro i in vivo metodama kroz nekolikostudija slučaja (ketoprofen, diklofenak dietilamin i hidrokortizon kao, Introduction Current pharmacoeconomic situation has resulted in a frequent shortagein certain drug doses/strengths or suitable dosage forms. The importance of theappropriate choice of the vehicle/base is especially emphasized in case of topical drugs.These are prone to influences stemming from the cosmetic industry, relating tosatisfactory appearance, texture and sensorial properties of the carrier, which directlyreflects patient adherence. Such drug deficiencies may be overcome throughcompounding practice in pharmacies which is, even in countries with highly developedpharmaceutical industry, reevaluating the importance of pharmacist’s knowledge andskills in extemporaneous drug preparation. Therefore, there is a need to innovate thecomposition of such drugs, particularly via introduction of formulations based on novelpharmaceutical excipients. On the other hand, the issue of dermal bioavailabilityassessment of these drugs remains, considering the regulatory accepted methods are notuniversally applicable (use of the skin blanching assay is limited to corticosteroid drugs)or their use is irrational in the formulation development phase (require substantial fundsand a large number of volunteers).Aim The aim of this work was the development, physicochemical andbiopharmaceutical characterization of emulsion systems (bases) stabilized with naturaloriginmixed alkyl polyglucoside (APG) emulsifier comprising cetostearyl glucosideand cetostearyl alcohol, recently given a status of pharmaceutical excipient. Theseformulations served as models for development and optimization of the tape strippingmethod protocol that could serve as a prospective in vivo technique for skin penetrationstudies, along with correlation of the obtained results with those provided through theacknowledged in vitro and in vivo methods via several case-studies (ketoprofen,diclofenac diethylamine and hydrocortisone as anti-inflammatory model drugs withdiverse physicochemical characteristics).Methods Experim

Uvod Aktuelna farmakoekonomska situacija ima za posledicu čest nedostatak lekova u potrebnim dozama/jačinama, a za neke lekovite supstance nisu odabrani pogodni nosači. Značaj primene odgovarajućeg vehikuluma/podloge naročito je izražen u slučaju lekova koji se primenjuju na koži. Ova grupa lekova podložna je i uticajima koji dolaze iz kozmetičke industrije, a odnose se na zadovoljavajući izgled, teksturu i senzorne karakteristike nosača, što se direktno reflektuje u kojoj meri će se pacijenti pridržavati propisanoj terapiji. Nedostatak lekova na tržištu može se prevazići izradom lekova u apoteci čime se, čak i u zemljama sa veoma razvijenom farmaceutskom industrijom, ponovo potencira značaj znanja i veština farmaceuta u ex tempore izradi lekova. Iz tog razloga, prepoznata je potreba za inoviranjem sastava takvih lekova, pre svega uvođenjem formulacija sa savremenim farmaceutskim ekscipijensima. S druge strane, ostaje otvoreno pitanje procene dermalne raspoloživosti ovakvih lekova, s obzirom da regulatorno prihvaćene metode nisu univerzalno primenljive (poput ograničene primenljivosti vazokonstriktornog testa na lekove iz grupe kortikosteroida) ili se smatraju neracionalnim u fazi razvoja formulacije (podrazumevaju značajna ulaganja i veliki broj ispitanika). Cilj istraživanja Cilj istraživanja ove disertacije bio je razvoj formulacije, fizičkohemijska i biofarmaceutska karakterizacija emulzionih sistema (podloga) stabilizovanih prirodnim mešanim emulgatorom tipa alkil poliglukozida (APG), sastava cetostearil glukozid i cetostearil alkohol, koji je od skora sertificiran kao farmaceutski ekscipijens. Razvijene formulacije poslužile su kao modeli za razvoj i optimizaciju protokola metode sa adhezivnim trakama (tape stripping metode) kao perspektivne in vivo tehnike za ispitivanje penetracije lekova kroz kožu, uz sprovođenje korelacije datih rezultata sa onim dobijenim prihvaćenim in vitro i in vivo metodama kroz nekoliko studija slučaja (ketoprofen, diklofenak dietila, Introduction Current pharmacoeconomic situation has resulted in a frequent shortage in certain drug doses/strengths or suitable dosage forms. The importance of the appropriate choice of the vehicle/base is especially emphasized in case of topical drugs. These are prone to influences stemming from the cosmetic industry, relating to satisfactory appearance, texture and sensorial properties of the carrier, which directly reflects patient adherence. Such drug deficiencies may be overcome through compounding practice in pharmacies which is, even in countries with highly developed pharmaceutical industry, reevaluating the importance of pharmacist’s knowledge and skills in extemporaneous drug preparation. Therefore, there is a need to innovate the composition of such drugs, particularly via introduction of formulations based on novel pharmaceutical excipients. On the other hand, the issue of dermal bioavailability assessment of these drugs remains, considering the regulatory accepted methods are not universally applicable (use of the skin blanching assay is limited to corticosteroid drugs) or their use is irrational in the formulation development phase (require substantial funds and a large number of volunteers). Aim The aim of this work was the development, physicochemical and biopharmaceutical characterization of emulsion systems (bases) stabilized with naturalorigin mixed alkyl polyglucoside (APG) emulsifier comprising cetostearyl glucoside and cetostearyl alcohol, recently given a status of pharmaceutical excipient. These formulations served as models for development and optimization of the tape stripping method protocol that could serve as a prospective in vivo technique for skin penetration studies, along with correlation of the obtained results with those provided through the acknowledged in vitro and in vivo methods via several case-studies (ketoprofen, diclofenac diethylamine and hydrocortisone as anti-inflammatory model drugs with diverse physicochemical characte

The primary objective of this study was to investigate the influence of the oligochitosan-Eudragit (R) L100-55 polyelectrolyte complex (OCH-EL PEC) on the pH-sensitivity of Eudragit (R) L100-55-treated alginate-oligochitosan microparticles. In order to achieve this, three types of naproxen-loaded microparticles were prepared under mild and environmentally friendly conditions using a custom made device with coaxial air flow: Ca-alginate (Ca-ALG), alginate-oligochitosan (ALG-OCH) and alginate-oligochitosan-Eudragit (R) L100-55 (ALG-OCH-EL) microparticles. After drying, the microparticles were subjected to microscopic analysis, and physicochemical and biopharmaceutical characterization. The non-covalent interaction between OCH and EL and the formation of OCH-EL PEC during the preparation procedure of the particles were verified by thermal and FT-IR analysis. The obtained particles exhibited acceptable sphericity and surface roughness due to the presence of the drug crystals (Ca-ALG particles) and OCH-EL PEC (ALG-OCH-EL particles). It was found that reinforcement of the ALG-OCH particles with OCH-EL PEC had no significant effect on the relatively high encapsulation efficiencies (>74.4%). The results of drug release studies confirmed the ability of ALG-OCH PEC to sustain drug release at pH 6.8 and 7.4. However, this PEC showed enhanced sensitivity to an acidic environment and to simulated intestinal fluid (pH 6.8) after prior exposure to an acidic medium. Additional treatment of ALG-OCH particles with EL and formation of "sandwich" ALG-OCH-EL PEC was essential not only to improve stability and decrease drug release in acidic medium, but also to achieve sustained release after the pH of dissolution medium was raised to 6.8. The obtained results suggested that ALG-OCH-EL microparticles have promising potential as pH-sensitive multiparticulate drug carriers for oral delivery of NSAIDs.

Objectives: The aim of the presented work was to develop Ca-alginate microparticles for oral administration of naproxen reinforced with chitosan oligosaccharide (COS) with a special interest to examine the potential of COS for improvement of microparticles stability in simulated intestinal fluid (SIF). Method: Microparticles were prepared according to the two-step procedure using an air-jet device with varying calcium chloride and COS concentration in the gelling medium. All prepared microparticles were subjected to size determination, morphology, surface, and inner structure analysis by scanning electron microscopy (SEM), drug loading (DL) and encapsulation efficiency (EE), differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, in vitro swelling, and drug release studies. Results: In general, COS-treated microparticles were spherical in shape but somewhat deformed, exhibiting the surface roughness with the mean particle size less than 350 mu m. FT-IR and DSC studies confirmed the formation of polyelectrolyte complex (PEC) between alginate and COS, whereas chemical properties and crystalline state of naproxen were unaffected by the encapsulation process. Low naproxen solubility in the gelling medium and rapid entrapment resulted in high encapsulation efficiency (>80.0%). The results of swelling studies demonstrated that COS-treated particles were less sensitive to swelling and erosion in SIF in comparison to the nontreated particles. This resulted in prolonged drug release in SIF, which was dependent on the COS/alginate ratio. Conclusion: The obtained findings proved that COS could be used as an effective cross-linking agent for improvement of Ca-alginate microparticles stability in SIF, allowing prolonged release of the encapsulated drug after oral administration.

Recently, healthcare professionals again began realizing the benefits of preparing customized medications to meet specific patient needs. The objective of this work was to develop and evaluate simple pharmaceutical bases stabilized with natural-origin surfactant of alkyl polyglucoside (APG) type as prospective ready-to-use bases and compare them to widely used pharmacopoeial ones. Additionally, the ability of the formulated bases to sustain isopropyl alcohol was assessed as well as its influence on ketoprofen skin absorption (as a co-solvent and potential penetration enhancer). In order to evaluate the manifold characteristics a topical drug product should possess, a comprehensive characterization was performed using different techniques. Physicochemical characterization demonstrated satisfactory physical stability of APG-stabilized bases upon the addition of alcohol. In vitro release/permeation studies failed to show significant difference in ketoprofen liberation/permeation profiles from different bases. However, the extent of ketoprofen delivery in vivo was clearly increased from APG bases, relative to that obtained from pharmacopoeia quality one, implying a distinct influence of the emulsion systems' colloidal structures. Taking also into account the rheological behavior of APG bases, revealing their ameliorated sensory characteristics, it could be concluded that the investigated APG bases could be considered as preferential option in drug compounding related to the conventional ones.

Context: In this study an investigation of cationic surfactants-modified natural zeolites as drug formulation excipient was performed. Objective: The aim of this work was to carry out a study of the purified natural zeolitic tuff with high amount of clinoptilolite as a potential carrier for molecules of pharmaceutical interest. Materials and methods: Two cationic surfactants (benzalkonium chloride and hexadecyltrimethylammonium bromide) were used for modification of the zeolitic surface in two levels (equal to and twice as external cation-exchange capacity of the zeolitic tuff). Prepared samples were characterized by Fourier transform infrared spectroscopy, thermogravimetric, high-performance liquid chromatography analysis, and powder flow determination. Different surfactant/zeolite composites were used for additional investigation of three model drugs: diclofenac diethylamine, diclofenac sodium, and ibuprofen by means of adsorption isotherm measurements in aqueous solutions. Results: The modified zeolites with two levels of surfactant coverage within the short activation time were prepared. Determination of flow properties showed that modification of zeolitic surface reflected on powder flow characteristics. Investigation of the model drugs adsorption on the obtained composites revealed that a variation between adsorption levels was influenced by the surfactant type and the amount present at the surface of the composites. Discussion and conclusion: In vitro release profiles of the drugs from the zeolite-surfactant-drug composites revealed that sustained drug release could be attained over a period of 8 hours. The presented results for drug uptake by surfactant-zeolite composites and the afterward drug release demonstrated the potential use of investigated modified natural zeolite as excipients for advanced excipients in drug formulations.

Background: The potential for use of chitosan-treated alginate microparticles as a vehicle for oral phenytoin delivery has not been thoroughly exploited. Aim: We studied the influence of preparation procedure and chitosan type on physicochemical properties and release behavior of alginate-chitosan microparticles. Method: The total number of 24 microparticles formulations prepared by varying contents of calcium gelling ions and varying contents and type of chitosan was examined. As an additional variable, two different hardening times (1 and 24 hours) were employed. Possible interactions of components, surface morphology of microparticles as well as release profile of phenytoin were studied. Results: Both series of formulations with regard to hardening times, irrespective of the chitosan type and/or concentration employed appeared to be highly loaded with the model drug (above 90%). The drug release studies showed that the kinetics of phenytoin cannot be straightforwardly predicted based on the molecular weight of chitosan alone. On the other hand, prolonging the hardening time from 1 to 24 hours had significantly improved phenytoin kinetics, and gave rise to a formulation with the liberation half-time of about 2.5 hours. Conclusion: This study showed that the latter formulation is eligible for further modifications aimed at improving the regularity of phenytoin absorption.

There is a growing need for research into new skin- and environment-friendly surfactants. The aim of the study was to find out whether a combination of an alkylpolyglucoside natural surfactant with established pharmaceutical excipients could provide a solid pharmaceutical base with satisfied physical stability. The study was carried out in two phases: the first one focused on the colloidal structure of vehicles formulated with oils of different polarity and/or different costabilizer (lipophilic versus hydrophilic) and the second one evaluated vehicles' physical stability. A number of techniques were used (polarization, light, and transmission electron microscopy, pH, conductivity and thermogravimetric measurements, rheological analysis and cyclic temperature stress test). Natural surfactant's interaction with used excipients resulted in the formation of semisolid emulsion systems of different rheological profiles, stabilized predominantly by synergistic effects of lamellar liquid-crystalline (L) and complex lamellar gel (Lβ) phases. The type of used oil and costabilizer significantly influenced the colloidal structure of the vehicles, particularly in terms of water distribution mode and initial rheological performance as well as their physical stability. It was recommended that medium polar oils of ester type and lipophilic costabilizers, particularly long chain fatty alcohols, should be used in the formulation of stable alkylpolyglucoside-based topical vehicles.

The aim of this study Was to Examine the lyotropic potential of an alkylpolyglucoside mixed Emulsifier (Cetearyl Glucoside & Cetearyl alcohol), Which Belongs to the new generation of natural (sugar) surfactants, and to elaborate the stabilization mechanism and relation Between the colloid microstructure and water distribution Within the systems. Polarization and ordinary light as well as transmission electron microscopy, wide angle X-ray diffraction, thermal analysis and rheological measurement, as well as in vivo hydration potential Were employed for testing the systems Characterization. A comparison of results Obtained from Isothermal thermogravimetry and in vivo short-term application study served to Recognize Within water distribution systems and the dynamic of water evaporation, ie to consider in the Possibility of Formulation and Prolonged water emulsion with controlled release. It Was Suggested That Cetearyl glucoside & Cetearyl alcohol stabilizes the o / w creams by synergistic effects of Viscoelastic Hydrophilic Lamellar type of gel and lipophilic gel network built up from semi-Cetostearyl alcohol hydrates as well as by Lamellar liquid crystalline bilayers surrounding the oil droplets. Generally, in creams based on the non-ionic Emulsifier alkylpolyglucoside MontanovÒ 68 PHA four fractions of water Could Be Met: 1) free - bulk water, 2) Within lipophilic gel bonded water (secondary water), 3) water interlamelarilly Between fixed crystalline lipid bilayers (Hydrophilic gel) and 4) water Between fixed lipid layers in liquid-crystalline state. It is Also Showed That Additions oil into The Chosen binary system microstructure Significantly Influences the creams, Which Reflects Particularly onto the mode of water distribution and consequently Their creams Within The potential of skin hydration. Thus, the model with Emulsifier cream / water ratio of 1:10:43 and 20% medium chain triglycerides as oil phase Was selected as optimal model Formulation with Prolonged pro